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Randomized Controlled Trial
. 2015 Aug;160(2):313-321.e19.
doi: 10.1016/j.ajo.2015.04.025. Epub 2015 Apr 20.

Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study

Peter A Campochiaro  1 , Gulnar Hafiz  2 , Tahreem A Mir  2 , Adrienne W Scott  2 , Raafay Sophie  2 , Syed M Shah  2 , Howard S Ying  2 , Lili Lu  2 , Connie Chen  2 , J Peter Campbell  2 , Saleema Kherani  2 , Ingrid Zimmer-Galler  2 , Adam Wenick  2 , Ian Han  2 , Yannis Paulus  2 , Akrit Sodhi  2 , Guohua Wang  2 , Jiang Qian  2
Affiliations
Randomized Controlled Trial

Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study

Peter A Campochiaro et al. Am J Ophthalmol. 2015 Aug.

Abstract

Purpose: To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO).

Design: Prospective, interventional case series.

Methods: Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay.

Results: Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P = .014 and P = .003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant.

Conclusions: Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

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Figures

Figure 1.
Figure 1.. Improvement in central subfield thickness (top) and best-corrected visual acuity (bottom) after injection of dexamethasone implant in patients with macular edema due to retinal vein occlusion.
Patients with macular edema due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) were given an intravitreous injection of a dexamethasone implant at baseline. Mean (±standard error of the mean) change from baseline central subfield thickness (CST, top) and mean (±standard error of the mean) change from baseline best-corrected visual acuity (BCVA, bottom) are shown at each study visit.
Figure 2.
Figure 2.. Correlation between reduction from baseline and week 4 in aqueous level of pentraxin 3 (top) or persephin (bottom) and reduction from baseline in excess foveal thickness after dexamethasone implant in patients with retinal vein occlusion.
Patients who had detectable levels of pentraxin 3 (top) or persephin (bottom) at baseline and week 4 had percentage reduction in protein level plotted versus percentage reduction in excess foveal thickness. Pearson Correlation Coefficient was 0.685 for pentraxin 3 (p=0.014) and 0.638 for persephin (p=0.003).
See this image and copyright information in PMC

Comment in

References

    1. Campochiaro PA, Hafiz G, Shah SM, et al. Ranibizumab for macular edema due to retinal vein occlusions; implication of VEGF as a critical stimulator. Molec Ther 2008;16(4):791–799. - PubMed
    1. Campochiaro PA, Hafiz G, Channa R, et al. Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusion: two-year outcomes. Ophthalmology 2010;117(12):2387–2394. - PubMed
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